Assessing risk for HIV infection among adolescent girls in South Africa: an evaluation of the VOICE risk score (HPTN 068)

INTRODUCTION: To maximize impact and minimize costs, antiretroviral pre-exposure prophylaxis (PrEP) interventions should be offered to those at highest risk for HIV infection. The risk score derived from the VOICE trial is one tool currently being utilized to determine eligibility in adolescent PrEP trials in sub-Saharan Africa. This study is aimed at evaluating the utility of the risk score in predicting HIV incidence among a cohort of adolescent girls in rural South Africa. METHODS: We utilized data from HIV Prevention Trials Network (HPTN) 068, a phase III randomized controlled trial conducted in rural Mpumalanga province, South Africa. School-attending young women aged 13 to 20 years were enrolled into the trial from 2011 to 2012 and followed for up to three years. A risk score based on individual-level risk factors measured at enrolment was calculated for HPTN 068 participants who completed a one-year follow-up visit and were HIV seronegative at enrolment. Possible scores ranged from 0 to 10. A proportional hazards model was then used to determine if risk score at enrolment was predictive of incident HIV infection at follow-up and an area under the curve analysis was used to examine the predictive ability of the score. RESULTS AND DISCUSSION: The risk score had limited variability in the HPTN 068 sample. Scores ≥5 identified 85% of incident infections from 94% of the sample, compared to the VOICE sample in which scores ≥5 identified 91% of incident infections from only 64% of participants. The risk score did not predict HIV incidence after one year of follow-up (hazard ratio = 1.029; 95% confidence interval (CI): 0.704, 1.503, p = .884) and showed poor predictive ability (area under the curve = 0.55; 95% CI: 0.44, 0.65). Certain individual risk factors that comprise the risk score may be context specific or not relevant for adolescent populations. Additional factors should be considered when assessing risk for the purposes of determining PrEP eligibility. CONCLUSIONS: The VOICE risk score demonstrated low utility to predict HIV incidence in the HPTN 068 sample. Findings highlight the need for an age and developmentally appropriate tool for assessing risk for HIV infection among adolescents. Use of the VOICE risk score for determining PrEP eligibility in younger populations should be carefully considered

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels. Methods: The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence. Results: A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001). Conclusions: There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention

Associations between friendship characteristics and HIV and HSV-2 status amongst young South African women in HPTN-068.

INTRODUCTION: Prevalence of HIV among young women in South Africa remains extremely high. Adolescent peer groups have been found to be an important influence on a range of health behaviours. The characteristics of young women's friendships might influence their sexual health and HIV risk via connections to sexual partners, norms around sexual initiation and condom use, or provision of social support. We investigated associations between young women's friendships and their Herpes Simplex Virus Type 2 (HSV-2) and HIV infection status in rural South Africa. METHODS: Our study is a cross-sectional, egocentric network analysis. In 2011 to 2012, we tested 13- to 20-year-old young women for HIV and HSV-2, and collected descriptions of five friendships for each. We generated summary measures describing friend socio-demographic characteristics and the number of friends perceived to have had sex. We used logistic regression to analyse associations between friend characteristics and participant HIV and HSV-2 infection, excluding likely perinatal HIV infections. RESULTS: There were 2326 participants included in the study sample, among whom HIV and HSV-2 prevalence were 3.3% and 4.6% respectively. Adjusted for participant and friend socio-demographic characteristics, each additional friend at least one year older than the participant was associated with raised odds of HIV (odds ratio (OR) = 1.37, 95% CI 1.03 to 1.82) and HSV-2 (adjusted OR=1.41, 95% CI 1.18 to 1.69). Each additional friend perceived to have ever had sex also raised the odds of HIV (OR = 1.29, 95% CI 1.03 to 1.63) and HSV-2 (OR=1.18, 95% CI 1.03 to 1.35). DISCUSSION: We found good evidence that a greater number of older friends and friends perceived to have had sex were associated with increased risk for HSV-2 and HIV infection among young women. CONCLUSIONS: The characteristics of young women's friendships could contribute to their risk of HIV infection. The extent to which policies or programmes influence age-mixing and young women's normative environments should be considered

The development and validation of a method using high-resolution mass spectrometry (HRMS) for the qualitative detection of antiretroviral agents in human blood

Antiretroviral drugs are used for the treatment and prevention of HIV infection. Non-adherence to antiretroviral drug regimens can compromise their clinical efficacy and lead to emergence of drug-resistant HIV. Clinical trials evaluating antiretroviral regimens for HIV treatment and prevention can also be compromised by poor adherence and non-disclosed off-study antiretroviral drug use. This report describes the development and validation of a high throughput, qualitative method for the identification of antiretroviral drugs using high-resolution mass spectrometry (HRMS) for the retrospective assessment of off-study antiretroviral drug use and the determination of potential antiretroviral therapy (ART) non-compliance

Incidence and correlates of STIs among black men who have sex with men participating in a US PrEP study

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Antiretroviral Therapy for the Prevention of HIV-1 Transmission

An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission

Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073

ABSTRACT Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection

PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention

Pre-exposure prophylaxis initiation and adherence among Black men who have sex with men (MSM) in three US cities: results from the HPTN 073 study

Abstract : Introduction: Randomized clinical trials have demonstrated the efficacy of antiretroviral pre-exposure prophylaxis (PrEP) in preventing HIV acquisition among men who have sex with men (MSM). However, limited research has examined initiation and adherence to PrEP among Black MSM (BMSM) in the United States (US) who are disproportionately represented among newly HIV infected and late to care individuals. This research reports on the HIV Prevention Trials Network 073 (HPTN 073) study aimed to examine PrEP initiation, utilization and adherence among Black MSM utilizing the theoretically principled, cul- turally informed and client-centered care coordination (C4) model. Methods: The HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles, CA; Washington DC; and Chapel Hill, NC) from February 2013 through September 2015. Study participants were offered once daily oral emtricitabine/tenofovir (FTC/TDF) PrEP combined with C4 and followed up for 52 weeks. Participants received HIV testing, risk reduction education and clinical monitoring. Results: Of the 226 men enrolled, 178 participants initiated PrEP (79%), and of these 64% demonstrated PrEP utilization at week 26 (mid-point of the study) based on pharmacokinetic testing. Condomless anal sex with an HIV-infected or unknown status casual male partner was statistically significantly associated with a greater likelihood of PrEP initiation (adjusted odds ratio (OR) 4.4, 95% confidence interval (CI) 1.7, 11.7). Greater age (≥25 vs. <25, OR 2.95, 95% CI 1.37 –6.37), perception of having enough money (OR 3.6, 95% CI 1.7 to 7.7) and knowledge of male partner taking PrEP before sex (OR 2.22, 95% CI 1.03 to 4.79) were statistically significantly associated with increased likelihood of PrEP adherence at week 26. Annualized HIV incidence was 2.9 (95% CI 1.2 to 7.9) among those who initiated PrEP, compared to 7.7 (95% CI 2.5 to 24.1) among those who did not initiate PrEP (p = 0.18). Conclusions: Results suggest a high level of PrEP initiation among at-risk Black MSM, a group historically characterized as hard to reach. The data support the importance of addressing contextual factors that affect PrEP initiation and adherence, and of additional research on the ultimate benefit of PrEP in HIV prevention among Black MSM

Determination of HIV status and identification of incident HIV infections in a large, community-randomized trial: HPTN 071 (PopART).

INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates